Hcl-gemcitabine | 701937-50-0

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: Hcl-gemcitabine
• 英文别名: 4-AMINO-1-[3,3-DIFLUORO-4-HYDROXY-5-HYDROXYMETHYL-TETRAHYDROFURAN-2-YL]-1H-PYRIMIDIN-2-ONE HYDROCHLORIDE；4-amino-1-[3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one;hydron;chloride
• CAS: 701937-50-0
• 化学式: C₉H₁₁F₂N₃O₄*ClH
• 分子量: 299.662
• InChiKey: OKKDEIYWILRZIA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.87
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  108
• 氢给体数：
  4
• 氢受体数：
  6

ADMET

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间使用总结：大多数来源认为，在母亲抗肿瘤药物治疗期间，母乳喂养是禁忌的。在间歇性吉西他滨治疗期间，如果有一个适当的禁乳期，可能可以安全地进行母乳喂养；制造商建议在最后一次给药后至少禁乳1周。化疗可能会不利地影响母乳的正常微生物组和化学成分。[1] 在怀孕期间接受化疗的妇女更有可能在哺乳婴儿时遇到困难。[2] ◉ 对哺乳婴儿的影响：截至修订日期，未找到相关已发布信息。 ◉ 对泌乳和母乳的影响：对74名在怀孕第二或第三季度在一个中心接受癌症化疗的妇女进行了电话随访研究，以确定她们产后是否成功进行母乳喂养。只有34%的妇女能够完全用母乳喂养她们的婴儿，而66%的妇女报告遇到母乳喂养困难。这与22位在怀孕期间被诊断但未接受化疗的母亲91%的母乳喂养成功率形成了对比。其他具有统计学意义的相关性包括：1. 有母乳喂养困难的母亲平均接受了5.5个周期的化疗，而没有困难的母亲平均接受了3.8个周期；2. 有母乳喂养困难的母亲在怀孕期间平均比没有困难的母亲早3.4周接受第一次化疗周期。在接受了含氟尿嘧啶方案的9名妇女中，有8名遇到了母乳喂养困难。[2]

◉ Summary of Use during Lactation:Most sources consider breastfeeding to be contraindicated during maternal antineoplastic drug therapy. It might be possible to breastfeed safely during intermittent gemcitabine therapy with an appropriate period of breastfeeding abstinence; the manufacturer recommends an abstinence period of at least 1 week after the last dose. Chemotherapy may adversely affect the normal microbiome and chemical makeup of breastmilk.[1] Women who receive chemotherapy during pregnancy are more likely to have difficulty nursing their infant.[2] ◉ Effects in Breastfed Infants:Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk:A telephone follow-up study was conducted on 74 women who received cancer chemotherapy at one center during the second or third trimester of pregnancy to determine if they were successful at breastfeeding postpartum. Only 34% of the women were able to exclusively breastfeed their infants, and 66% of the women reported experiencing breastfeeding difficulties. This was in comparison to a 91% breastfeeding success rate in 22 other mothers diagnosed during pregnancy, but not treated with chemotherapy. Other statistically significant correlations included: 1. mothers with breastfeeding difficulties had an average of 5.5 cycles of chemotherapy compared with 3.8 cycles among mothers who had no difficulties; and 2. mothers with breastfeeding difficulties received their first cycle of chemotherapy on average 3.4 weeks earlier in pregnancy. Of the 9 women who received a fluorouracil-containing regimen, 8 had breastfeeding difficulties.[2]

来源:Drugs and Lactation Database (LactMed)

反应信息

• 作为反应物：
  描述：

  Hcl-gemcitabine 、 叔丁基二苯基氯硅烷 在 咪唑 作用下， 以 DMF (N,N-dimethyl-formamide) 为溶剂， 反应 72.0h， 以81%的产率得到4-AMINO-1-[5-(TERT-BUTYLDIPHENYLSILYLOXYMETHYL)-3,3-DIFLUORO-4-HYDROXY-TETRAHYDROFURAN-2-YL]-1H-PYRIMIDIN-2-ONE
  参考文献：
  名称：

  [EN] SILICON COMPOUNDS
  [FR] COMPOSES DE SILICIUM

  摘要：

  化合物式为(I)的化合物，其中R1和R2中的一个是-Si(R)3，另一个是氢或-Si(R)3; 或者R1是键，R2是-Si(R)2-或-Si(R)2-O-Si(R)2-，并且R10-CH2-CH-CH-OR2在一起形成一个环; R3和R4相同或不同，均为卤素; 每个R相同或不同，是烷基，芳基，环烷基或杂环烷基; 或其药学上可接受的盐。

  公开号：

  WO2004050665A1

文献信息

• Efficient Click Synthesis of a Protonized and Reduction-Sensitive Amphiphilic Small-Molecule Prodrug Containing Camptothecin and Gemcitabine for a Drug Self-Delivery System
  作者：Shuxiang Dong、Jinlin He、Yue Sun、Dian Li、Lei Li、Mingzu Zhang、Peihong Ni

  DOI：10.1021/acs.molpharmaceut.9b00349

  日期：2019.9.3

  work, we proposed a highly efficient strategy to fabricate protonized and reduction-responsive self-assembled drug nanoparticles from an amphiphilic small-molecule camptothecin-ss-1,2,3-triazole-gemcitabine conjugate (abbreviated as CPT-ss-triazole-GEM) for combination chemotherapy, which was prepared via a Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) "click" reaction. To obtain this drug-triazole-drug

  近来，由具有用于细胞内递送的纳米级特征的小分子活性药物组成的药物自递送系统引起了很多关注。在这项工作中，我们提出了一种高效的策略，可从两亲性小分子喜树碱-ss-1,2,3-三唑-吉西他滨偶联物（缩写为CPT-ss-三唑）制备质子化且具有还原反应的自组装药物纳米颗粒-GEM）用于联合化疗，这是通过Cu（I）催化的叠氮化物-炔烃环加成（CuAAC）“点击”反应制备的。为了获得这种药物-三唑-药物缀合物，我们首先制备了CPT衍生物，其含有与二硫键相连的炔丙基和与叠氮基相连的GEM衍生物。随后，两种修饰的药物通过炔基和叠氮基之间的CuAAC反应连接在一起，生成CPT-ss-三唑-GEM前药。这些中间体和最终产物的化学结构的表征是通过1 H NMR，傅立叶变换红外光谱和液相色谱/质谱法进行的。该两亲性小分子药物-三唑-药物偶联物显示出高的药物载量含量，即CPT的36.0％和GEM的27.2％。这种两
• [EN] SILICON COMPOUNDS<br/>[FR] COMPOSES DE SILICIUM
  申请人：AMEDIS PHARM LTD

  公开号：WO2004050665A1

  公开（公告）日：2004-06-17

  A compound of formula (I) wherein one of R1 and R2 is -Si(R)3, and the other is hydrogen or -Si(R)3; or R1 is a bond, R2 is -Si(R)2- or -Si(R)2 -O-Si(R)2-, and R10-CH2-CH-CH-OR2 taken together form a ring; R3 and R4 are the same or different and are each halogen; and each R is the same or different and is alkyl, aryl, cycloalkyl or heterocycloalkyl; or a pharmaceutically acceptable salt thereof.

  化合物式为(I)的化合物，其中R1和R2中的一个是-Si(R)3，另一个是氢或-Si(R)3; 或者R1是键，R2是-Si(R)2-或-Si(R)2-O-Si(R)2-，并且R10-CH2-CH-CH-OR2在一起形成一个环; R3和R4相同或不同，均为卤素; 每个R相同或不同，是烷基，芳基，环烷基或杂环烷基; 或其药学上可接受的盐。

表征谱图